Social epigenetics of Alzheimer's disease and related dementias in Latin American countries

Summary: Research suggests that alterations in epigenetics in immune cells may provide a causal link between Social Determinants of Health (SDH) adversity and health disparity through alterations at genome regulation in stress, inflammation, and cardiometabolic genes. Negative SDH are exacerbated in diverse populations and create health inequities hypothesized to occur through epigenetic changes. While social epigenomics research is expanding in high-income countries, the link between SDH and epigenetic changes has not been studied in LAC. Moreover, whether the connection between SDH and DNAm patterns influences dementia risk and its presentation remains a map gap in knowledge. In this research proposal we will study the epigenetic changes associated with negative SDH in patients with Alzheimer¿s disease (AD) and Frontotemporal dementia (FTD) in countries with different social risks levels in Latin America. To this end, we will leverage the NIH funded Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLaT) cohort20 study of AD and FTD patients and healthy controls from countries with different SDH levels, including a low-income country (Colombia), a middle-income country (Argentina), and high-income countries (Chile and the US) reaching a total sample of 900 individuals (300 AD, 300 FTD, and 300 Controls). In this research proposal we will test the hypothesis that a social adversity-epigenetic signature at regulatory regions of proinflammatory, stress, and cardiometabolic genes associates with dementia presentation and heterogeneity in Latinos.